Baicalin reduces chronic stress-induced breast cancer metastasis via directly targeting β2-adrenergic receptor

Qi Jia; Yinyin Zhou; Li Song; Ximeng Shi; Xuan Jiang; Ruizhi Tao; Aiyun Wang; Yuanyuan Wu; Zhonghong Wei; Yinan Zhang; Xiaoman Li; Yin Lu

doi:10.1016/j.jpha.2024.01.002

Volume 14 Issue 7

Jul. 2024

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Article Navigation > Journal of Pharmaceutical Analysis > 2024 > 14(7): 100934

Qi Jia, Yinyin Zhou, Li Song, Ximeng Shi, Xuan Jiang, Ruizhi Tao, Aiyun Wang, Yuanyuan Wu, Zhonghong Wei, Yinan Zhang, Xiaoman Li, Yin Lu. Baicalin reduces chronic stress-induced breast cancer metastasis via directly targeting β2-adrenergic receptor[J]. Journal of Pharmaceutical Analysis, 2024, 14(7): 100934. doi: 10.1016/j.jpha.2024.01.002

Citation:

Qi Jia, Yinyin Zhou, Li Song, Ximeng Shi, Xuan Jiang, Ruizhi Tao, Aiyun Wang, Yuanyuan Wu, Zhonghong Wei, Yinan Zhang, Xiaoman Li, Yin Lu. Baicalin reduces chronic stress-induced breast cancer metastasis via directly targeting β2-adrenergic receptor[J]. Journal of Pharmaceutical Analysis, 2024, 14(7): 100934. doi: 10.1016/j.jpha.2024.01.002

Citation:

Qi Jia, Yinyin Zhou, Li Song, Ximeng Shi, Xuan Jiang, Ruizhi Tao, Aiyun Wang, Yuanyuan Wu, Zhonghong Wei, Yinan Zhang, Xiaoman Li, Yin Lu. Baicalin reduces chronic stress-induced breast cancer metastasis via directly targeting β2-adrenergic receptor[J]. Journal of Pharmaceutical Analysis, 2024, 14(7): 100934. doi: 10.1016/j.jpha.2024.01.002

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Baicalin reduces chronic stress-induced breast cancer metastasis via directly targeting β2-adrenergic receptor

doi: 10.1016/j.jpha.2024.01.002

Qi Jia^a,
Yinyin Zhou^a,
Li Song^a,
Ximeng Shi^d,
Xuan Jiang^a,
Ruizhi Tao^a,
Aiyun Wang^a,b,c,
Yuanyuan Wu^a,
Zhonghong Wei^a,
Yinan Zhang^{d
,
,},
Xiaoman Li^{a
,
,},
Yin Lu^{a,b,c
,
,}

a. Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China;
b. Jiangsu Joint International Research Laboratory of Chinese Medicine and Regenerative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China;
c. Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine (TCM) Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing, 210023, China;
d. Jiangsu Key Laboratory for Functional Substances of Chinese Medicine, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China

Funds:

This work was supported by the Matching Grant of National Natural Science Foundation of China from Nanjing University of Chinese Medicine (Grant Nos.: NZY81903857, and NZY81703765), the National Natural Science Foundation of China (Grant No.: 21877062), the Opening Project of Chinese Materia Medica First-Class Discipline of Nanjing University of Chinese Medicine (Grant No.: 2020YLXK020), and Postgraduate Research & Practice Innovation Program of Jiangsu Province (Grant Nos.: SJCX21_0707, KYCX21_1772, and KYCX22_2039).

Received Date: Sep. 08, 2023
Accepted Date: Jan. 02, 2024
Rev Recd Date: Dec. 13, 2023
Publish Date: Jan. 04, 2024

Abstract

Abstract

Recent studies have shown that stress can substantially facilitate breast cancer metastasis, which can be reduced by nonselective β1/β2-adrenergic receptor (β1/β2-AR) blocker. However, several side effects were identified. Thus, it is extremely warranted to explore more effective and better-tolerated β2-AR blocker. Currently, we demonstrated that baicalin (BA), a major bioactive component of Scutellaria baicalensis Georgi, could significantly attenuate stress hormones especially epinephrine (Epi)-induced breast cancer cell migration and invasion in vitro. Mechanistically, we identified that β2-AR was a direct target of BA via the drug affinity responsive target stability (DARTS) combined with mass spectrum assay, and BA photoaffinity probe with pull-down assay, which was further confirmed by a couple of biophysical and biochemical assays. Furthermore, we demonstrated that BA could directly bind to the Phe-193 and Phe-289 of β2-AR, subsequently inhibit cyclic adenosine monophosphate-protein kinase A-focal adhesion kinase (cAMP-PKA-FAK) pathway, and thus impede epithelial-mesenchymal transition (EMT), thereby hindering the metastatic progression of the chronic stress coupled with syngeneic and xenograft in vivo orthotopic and tail vein mouse model. These findings firstly identify BA as a potential β2-AR inhibitor in the treatment of stress-induced breast cancer metastasis.
- Baicalin,
- Chronic stress,
- Breast cancer metastasis,
- β2-adrenergic receptor,
- Epithelial-mesenchymal transition

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References(53)

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